According to data from the World Health Organization, Italy has been particularly affected by the ongoing COVID‐19 pandemic. On April 1st 2020, Italy gained, at a world level, the highest number of total confirmed cases (n=110,574) and deaths (n=13,155) since the beginning of the outbreak. The number of cases raised exponentially, reaching a total of 227,364 infected subjects and 32,330 deaths on May, 20. The distribution of infected subjects and deaths, however, was not homogeneous, being respectively about 7‐times and 12‐times higher in northern‐ than in southern regionsMast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate.In December 2019, a novel coronavirus pneumonia, coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) was reported in Wuhan, China. A hyperinflammatory immune response, or cytokine release syndrome (CRS) is observed in critically unwell patients with SARS‐CoV‐2 globally. Severe lymphopenia, hyperactivated pro‐inflammatory T cells1 and decreased regulatory T cells2 are seen in these critically ill patients, suggesting dysregulated immune responses.Cholestatic liver diseases result in the hepatic retention of bile acids, causing subsequent liver toxicity. Peroxisome proliferator-activated receptor alpha (PPARα) regulates bile acid metabolism. In this retrospective observational study, we assessed the effects of fenofibrate (a PPARα agonist) therapy on bile acid metabolism when given to patients with PBC and PSC who have had an incomplete response to Ursodiol monotherapy. When fenofibrate was added to Ursodiol therapy there was a significant reduction and in some cases normalization of serum ALP, ALT, and AST abnormalities, as well as pro-inflammatory cytokines. Combination fenofibrate treatment also reduced 7α-hydroxy-4-cholesten-3-one (C4), the bile acid precursor, as well as total, primary, and conjugated bile acids. https://www.selleckchem.com/ In addition, principal components analysis and heatmap analysis show that bile acid metabolites trended closer to that of healthy control subjects. These favorable effects of fenofibrate on bile acid metabolism may contribute to its beneficial clinical effects in patients with PBC and PSC experiencing a sub-therapeutic response to Ursodiol monotherapy.The SARS-CoV-2-associated disease (COVID-19) is primarily manifested as a respiratory tract infection but may affect and cause complications from multiple organ systems (cardiovascular, gastrointestinal, kidneys, hematopoietic and immune systems) while no proven specific therapy exists. The challenges associated with COVID-19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID-19 may be particularly challenging in patients with AL amyloidosis who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, AL patients may be more susceptible to toxicities of drugs used to manage COVID-19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences, treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.Some diseases can be cured by medical interventions, others not. When not, are there other approaches to control or cure? One possibility is to try to publish a disease to death, a therapy strategy first proposed by my late colleague Prof. David Golde from UCLA (see below). Here I consider whether this strategy is working in the fight against severe acute respiratory syndrome-cornavirsu-2 (SARS-CoV-2) pandemic and the associated coronavirus infectious disease-2019 (COVID-19).SARS‐CoV‐2 is spreading worldwide, and is a pandemic virus that has infected almost 5 million individuals and causing 300.000 deaths, as of mid‐May 2020. Because SARS‐CoV‐2 is a new virus in humans there are currently no vaccines, monoclonal antibodies (mAbs) or even effective drugs available. Human convalescent plasma transfusion is an option for either prophylactic or therapeutic treatment of COVID‐19 patients, but its administration to patients who are affected by severe pulmonary disease is associated with increased risk of transfusion‐related acute lung injury (TRALI).Background von Willebrand factor (VWF) is crucial for optimal dosing of factor VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, it is unknown how VWF behaves and what its impact is on FVIII clearance in the perioperative setting. Aim To investigate VWF kinetics (VWF antigen [VWFAg]), VWF glycoprotein Ib binding (VWFGPIbM), and VWF propeptide (VWFpp) in severe and moderate perioperative hemophilia A patients included in the randomized controlled perioperative OPTI-CLOT trial. Methods Linear mixed effects modeling was applied to analyze VWF kinetics. One-way and two-way analyses of variance were used to investigate perioperative VWFpp/VWFAg ratios and associations with surgical bleeding. Results Fifty-nine patients with median age of 48.8 years (interquartile range 34.8-60.0) were included. VWFAg and VWFGPIbM increased significantly postoperatively. Blood type non-O or medium risk surgery were associated with higher VWFAg and VWFGPIbM levels compared with blood type O and low risk surgery.